mig-38, a novel gene that regulates distal tip cell turning during gonadogenesis in C. elegans hermaphrodites

摘要

InemCaenorhabditiselegans/emgonadmorphogenesis,thefinalU-shapesofthetwohermaphroditegonadarmsaredeterminedbymigrationofthedistaltipcells(DTCs).Thesesomaticcellsmigrateinoppositedirectionsontheventralbasementmembraneuntilspecificextracellularcuesinduceturningfromventraltodorsalandthencentripetallytowardthemidbodyregiononthedorsalbasementmembrane.TodissectthemechanismofDTCturning,weexaminedtheroleofanovelgene,emF40F11.2/mig-38/em,whosedepletionbyRNAiresultsinfailureofDTCturningsothatDTCscontinuetheirmigrationawayfromthemidbodyregion.emmig-38/emisexpressedinthegonadprimordium,andexpressioncontinuesthroughoutDTCmigrationwhereitactscell-autonomouslytocontrolDTCturning.RNAidepletionofbothemmig-38/emandemina-1/em,whichencodesanintegrinadhesionreceptor,enhancedthelossofturningphenotypeindicatingageneticinteractionbetweenthesegenes.Furthermore,theintegrin-associatedproteinMIG-15em//emNck-interactingkinase(NIK)workswithMIG-38todirectDTCturningasshownbyemmig-38/emRNAiwiththeemmig-15/em(emrh80/em)hypomorph.TheseresultsindicatethatMIG-38enhancestheroleofMIG-15inintegrin-dependentDTCturning.Knockdownoftalin,aproteinthatisimportantforintegrinactivation,causestheDTCstostopmigrationprematurely.WhenbothtalinandMIG-38weredepletedbyRNAitreatment,theprematurestopphenotypewassuppressed.ThissuppressioneffectwasreverseduponadditionaldepletionofMIG-15oritsbindingpartnerNCK-1.TheseresultssuggestthatbothtalinandtheMIG-15/NCK-1complexpromoteDTCmotilityandthatMIG-38mayactasanegativeregulatorofthecomplex.WeproposeamodeltoexplainthedualroleofMIG-38inmotilityandturning./p/div